Given the widespread use of cannabis, increasing recognition of the potential health effects of this drug and a growing recognition of cannabis dependence as a distinct clinical entity, this resubmission of a previously reviewed application seeks funding to conduct a genetically informative research study of the assessment of cannabis use disorders, stages of development in and escalation of cannabis and the development of cannabis use disorders, and the mental health correlates of cannabis use, including escalation to the use of other drugs. The project will interview a sample of 6,600 young adult Australian twins using a structured interview assessing lifetime history of cannabis and other drug use and use disorders, and related aspects of substance use and mental health. Specific aims are: AIM 1: To examine the links (genetic or environmental) between early cannabis use and escalation both to the use of other drugs (cocaine, amphetamines, heroin and other opioids, sedatives, hallucinogens, ecstasy) and to drug abuse/ dependence. AIM 2: To assess the psychometric properties of an assessment of cannabis use disorders within the context of a genetically informative research design; and to examine the extent to which early onset cannabis use may be differentially associated with specific components of abuse/ dependence via genetic versus environmental mechanisms. AIM 3: To examine whether apparent links between early cannabis use and subsequent illicit drug use and abuse/ dependence can be explained by hypothesized social factors including exposure opportunity and the nature of peer affiliations at the time of initiation to cannabis use (reported retrospectively). AIM 4: To explore the links (genetic or environmental) between cannabis use and dependence and other measures of common mental health problems (major depressive disorder, persistent suicidal ideation, suicide attempt) and, in particular, to examine the extent to which continued or escalating cannabis use may exacerbate pre-existing mental health problems.